• Fig. 33.20 Cellular mechanism whereby an increase in delivery of NaCl to the macula densa causes vasoconstriction of the afferent arteriole of the same nephron (i.e., tubuloglomerular feedback). An increase in GFR elevates [NaCl] in tubule fluid at the macula densa. This in turn enhances uptake of NaCl across the apical cell membrane of macula densa cells via the 1Na+-1K+-2Cl− (NKCC2) symporter, which leads to an increase in [ATP] and [adenosine] (ADO) release. ATP binds to P2X receptors and adenosine binds to adenosine A1 receptors in the plasma membrane of smooth muscle cells surrounding the afferent arteriole, both of which increase intracellular [Ca++]. The rise in [Ca++] induces vasoconstriction of the afferent arteriole, thereby returning GFR to normal levels. Note that ATP and adenosine also inhibit renin release by granular cells in the afferent arteriole. This too results from an increase in intracellular [Ca++] as a reflection of electrical coupling of the granular and vascular smooth muscle (VSM) cells. When GFR is reduced, [NaCl] in tubule fluid falls, as does uptake of NaCl into macula densa cells. This in turn decreases release of ATP and adenosine by the macula densa, which decreases intracellular [Ca++] in smooth muscle cells and thereby increases GFR and stimulates renin release by granular cells. In addition a decrease in entry of NaCl into macula densa cells enhances production of PGE2, which also stimulates renin secretion by granular cells. As discussed in detail in , renin increases plasma [angiotensin II], a hormone that enhances NaCl and water retention by the kidneys. (Modified from Persson AEG et al. Acta Physiol Scand 2004;181:471.) 2.
Autoregulation is not perfect; RBF and GFR do change slightly as arterial blood pressure varies.
3.
Despite autoregulation, RBF and GFR can be changed by several hormones and by alterations in sympathetic nerve activity that change in response to alterations in the extracellular fluid volume (ECFV) (
Table 33.1
Regulation of Renal Blood Flow and Glomerular Filtration Rate
Table 33.1 ). As already discussed, the myogenic mechanism and tubuloglomerular feedback play key roles in maintaining RBF and GFR constant when blood pressure is greater that 90 mm Hg and ECFV is in the normal range. However, when the ECFV changes sympathetic nerves, angiotensin II, prostaglandins, NO, endothelin, bradykinin, ATP, and adenosine exert major control over RBF and GFR.
Fig.
33.21 shows how changes in efferent and afferent arteriolar resistance, mediated by changes in the hormones listed in
Table 33.1 , modulate both RBF and GFR.
The afferent and efferent arterioles are innervated by sympathetic neurons; however, sympathetic tone is minimal when ECFV is normal (see ). When ECFV is reduced, sympathetic nerves release norepinephrine and dopamine, and circulating epinephrine (a catecholamine-like norepinephrine and dopamine) is secreted by the adrenal medulla. Norepinephrine and epinephrine cause vasoconstriction by
Sympathetic nerves ↓ ECFV ↓↓ Angiotensin II ↓ ECFV ↓↓ Endothelin ↑ Stretch, A-II, bradykinin, epinephrine; ↓ ECFV ↓↓
Prostaglandins (PGE1, PGE2, PGI2) ↓ ECFV; ↑ shear stress, A-II No change/↑↑ Nitric oxide (NO) ↑ Shear stress, acetylcholine, histamine, bradykinin, ↑↑